tbuckley/cabot-search huggingface dataset:
Current evidence and the potential role of proton beam therapy for hepatocellular carcinoma
Authors: Sung Uk Lee, Tae Hyun Kim
Journal: Clinical and Molecular Hepatology (2023)

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, and external beam radiation therapy has emerged as a promising approach for managing HCC. Proton beam therapy (PBT) offers dosimetric advantages over X-ray therapy, with superior physical properties known as the Bragg peak. PBT holds promise for reducing hepatotoxicity and allowing safe dose-escalation to the tumor. It has been tried in various clinical conditions and has shown promising local tumor control and survival outcomes. A recent phase III trial demonstrated the non-inferiority of PBT in local tumor control compared to current standard radiofrequency ablation in early-stage HCC. PBT also tended to show more favorable outcomes compared to transarterial chemoembolization in the intermediate stage, and has proven effective in-field disease control and safe toxicity profiles in advanced HCC. In this review, we discuss the rationale, clinical studies, optimal indication, and future directions of PBT in HCC treatment.
<scp>UCRAID</scp> (Ukrainian Citizen and refugee electronic support in Respiratory diseases, Allergy, Immunology and Dermatology) action plan
Authors: Jean Bousquet, Boleslaw Samolinski, Igor Kaidashev, Marcus Maurer, Nicolas Roche, Bernardo Sousa‐Pinto, Andrii Kurchenko, Roman Stepanenko, Vladyslav Tsaryk, Ludger Klimek, Maria Teresa Ventura, Anna Bedbrook, Wienczyslawa Czarlewski, Yuliia Lysanets, Maciej Kupczyk, Łukasz Skolimowski, Marek Kulus, Stefano Del Giacco, Markus Ollert, Judith Garcia‐Aymerich, Carlos Robalo Cordeiro, Arzu Yorgancioglu, Christoph Schlapbach, Rita Amaral, Cristina Bonaglia, Isabelle Bossé, Rosalba Buquicchio, Demetrios Christou, Galyna Fedoruk, Pietro Fontanesi, Bilun Gemicioglu, Antonio F. M. Giuliano, Paolo Lepore, Alla Nakonechna, Sophia Neisinger, Ana M. Pereira, Aiste Ramanauskaite, Filip Raciborski, Brigita Sitkauskiene, Oksana Sokhatska, Viktor Stepanenko, Katarina Stevanovic, Orysya Syzon, Violeta Kvedariene, Govert de Vries, Michiel van Eerd, Arunas Valiulis, Joao A. Fonseca, Josep M. Anto, Tari Haahtela, Holger Schünemann, Torsten Zuberbier
Journal: Allergy (2023)

Abstract Eight million Ukrainians have taken refuge in the European Union. Many have asthma and/or allergic rhinitis and/or urticaria, and around 100,000 may have a severe disease. Cultural and language barriers are a major obstacle to appropriate management. Two widely available mHealth apps, MASK‐air® (Mobile Airways Sentinel NetworK) for the management of rhinitis and asthma and CRUSE® (Chronic Urticaria Self Evaluation) for patients with chronic spontaneous urticaria, were updated to include Ukrainian versions that make the documented information available to treating physicians in their own language. The Ukrainian patients fill in the questionnaires and daily symptom‐medication scores for asthma, rhinitis (MASK‐air) or urticaria (CRUSE) in Ukrainian. Then, following the GDPR, patients grant their physician access to the app by scanning a QR code displayed on the physician's computer enabling the physician to read the app contents in his/her own language. This service is available freely. It takes less than a minute to show patient data to the physician in the physician's web browser. UCRAID—developed by ARIA (Allergic Rhinitis and its Impact on Asthma) and UCARE (Urticaria Centers of Reference and Excellence)—is under the auspices of the Ukraine Ministry of Health as well as European (European Academy of Allergy and Clinical immunology, EAACI, European Respiratory Society, ERS, European Society of Dermatologic Research, ESDR) and national societies.
Rare Variant Genetics and Dilated Cardiomyopathy Severity: The DCM Precision Medicine Study
Authors: Mark Hofmeyer, Garrie J. Haas, Elizabeth Jordan, Jinwen Cao, Evan Kransdorf, Gregory A. Ewald, Alanna A. Morris, Anjali Owens, Brian Lowes, Douglas Stoller, W.H. Wilson Tang, Sonia Garg, Barry H. Trachtenberg, Palak Shah, Salpy V. Pamboukian, Nancy K. Sweitzer, Matthew T. Wheeler, Jane E. Wilcox, Stuart Katz, Stephen Pan, Javier Jimenez, Frank Smart, Jessica Wang, Stephen S. Gottlieb, Daniel P. Judge, Charles K. Moore, Gordon S. Huggins, Daniel D. Kinnamon, Hanyu Ni, Ray E. Hershberger
Journal: Circulation (2023)

BACKGROUND: Dilated cardiomyopathy (DCM) can lead to advanced disease, defined herein as necessitating a durable left ventricular assist device or a heart transplant (LVAD/HT). DCM is known to have a genetic basis, but the association of rare variant genetics with advanced DCM has not been studied. METHODS: We analyzed clinical and genetic sequence data from patients enrolled between 2016 and 2021 in the US multisite DCM Precision Medicine Study, which was a geographically diverse, multiracial, multiethnic cohort. Clinical evaluation included standardized patient interview and medical record query forms. DCM severity was classified into 3 groups: patients with advanced disease with LVAD/HT; patients with an implantable cardioverter defibrillator (ICD) only; or patients with no ICD or LVAD/HT. Rare variants in 36 DCM genes were classified as pathogenic or likely pathogenic or variants of uncertain significance. Confounding factors we considered included demographic characteristics, lifestyle factors, access to care, DCM duration, and comorbidities. Crude and adjusted associations between DCM severity and rare variant genetic findings were assessed using multinomial models with generalized logit link. RESULTS: Patients’ mean (SD) age was 51.9 (13.6) years; 42% were of African ancestry, 56% were of European ancestry, and 44% were female. Of 1198 patients, 347 had LVAD/HT, 511 had an ICD, and 340 had no LVAD/HT or ICD. The percentage of patients with pathogenic or likely pathogenic variants was 26.2%, 15.9%, and 15.0% for those with LVAD/HT, ICD only, or neither, respectively. After controlling for sociodemographic characteristics and comorbidities, patients with DCM with LVAD/HT were more likely than those without LVAD/HT or ICD to have DCM-related pathogenic or likely pathogenic rare variants (odds ratio, 2.3 [95% CI, 1.5–3.6]). The association did not differ by ancestry. Rare variant genetic findings were similar between patients with DCM with an ICD and those without LVAD/HT or ICD. CONCLUSIONS: Advanced DCM was associated with higher odds of rare variants in DCM genes adjudicated as pathogenic or likely pathogenic, compared with individuals with less severe DCM. This finding may help assess the risk of outcomes in management of patients with DCM and their at-risk family members. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03037632.
Neutrophils for Revascularization Require Activation of CCR6 and CCL20 by TNFα
Authors: Holger Lörchner, Laia Cañes Esteve, Maria Elisa Góes, Roxanne Harzenetter, Nathalie Brachmann, Praveen Gajawada, Stefan Günther, Nicolas Doll, Jochen Pöling, Thomas Braun
Journal: Circulation Research (2023)

Activation of immune-inflammatory pathways involving TNFα (tumor necrosis factor alpha) signaling is critical for revascularization and peripheral muscle tissue repair after ischemic injury. However, mechanisms of TNFα-driven inflammatory cascades directing recruitment of proangiogenic immune cells to sites of ischemia are unknown.Muscle tissue revascularization after permanent femoral artery ligation was monitored in mutant mice by laser Doppler imaging and light sheet fluorescence microscopy. TNFα-mediated signaling and the role of the CCL20 (C-C motif chemokine ligand 20)-CCR6 (C-C chemokine receptor 6) axis for formation of new vessels was studied in vitro and in vivo using bone marrow transplantation, flow cytometry, as well as biochemical and molecular biological techniques.TNFα-mediated activation of TNFR (tumor necrosis factor receptor) 1 but not TNFR2 was found to be required for postischemic muscle tissue revascularization. Bone marrow-derived CCR6+ neutrophil granulocytes were identified as a previously undescribed TNFα-induced population of proangiogenic neutrophils, characterized by increased expression of VEGFA (vascular endothelial growth factor A). Mechanistically, postischemic activation of TNFR1 induced expression of the CCL20 in vascular cells and promoted translocation of the CCL20 receptor CCR6 to the cell surface of neutrophils, essentially conditioning VEGFA-expressing proangiogenic neutrophils for CCL20-dependent recruitment to sites of ischemia. Moreover, impaired revascularization of ischemic peripheral muscle tissue in diabetic mice was associated with reduced numbers of proangiogenic neutrophils and diminished CCL20 expression. Administration of recombinant CCL20 enhanced recruitment of proangiogenic neutrophils and improved revascularization of diabetic ischemic skeletal muscles, which was sustained by sequential treatment with fluvastatin.We demonstrate that site-specific activation of the CCL20-CCR6 axis via TNFα recruits proangiogenic VEGFA-expressing neutrophils to sites of ischemic injury for initiation of muscle tissue revascularization. The findings provide an attractive option for tissue revascularization, particularly under diabetic conditions.
Association between epicardial adipose tissue and cardiac dysfunction in subjects with severe obesity
Authors: Jie Fen Chin, Yaar S. Aga, S. Abou Kamar, D. Kroon, Sanne M. Snelder, Sweder W.E. van de Poll, Isabella Kardys, Jasper J. Brugts, Rudolf A. de Boer, Bas M. van Dalen
Journal: European Journal of Heart Failure (2023)

Epicardial adipose tissue (EAT) plays a role in obesity-related heart failure with preserved ejection fraction. However, the association of EAT thickness with the development of cardiac dysfunction in subjects with severe obesity without known cardiovascular disease is unclear. The aim of this study was to determine the association between EAT thickness and cardiac dysfunction and describe the potential value of EAT as an early marker of cardiac dysfunction.Subjects with body mass index ≥35 kg/m2 aged 35 to 65 years, who were referred for bariatric surgery, without suspicion of or known cardiac disease, were enrolled. Conventional transthoracic echocardiography and strain analyses were performed. A total of 186 subjects were divided into tertiles based on EAT thickness, of whom 62 were in EAT-1 (EAT <3.8 mm), 63 in EAT-2 (EAT 3.8-5.4 mm), and 61 in EAT-3 (EAT >5.4 mm). Parameters of systolic and diastolic function were comparable between tertiles. Patients in EAT-3 had the lowest global longitudinal strain (GLS) and left atrial contractile strain (LASct). Linear regression showed that a one-unit increase in EAT thickness (mm) was independently associated with a decrease in GLS (%) (β coefficient -0.404, p = 0.002), and a decrease in LASct (%) (β coefficient -0.544, p = 0.027). Furthermore, EAT-3 independently predicted cardiac dysfunction as defined by a GLS <18% (odds ratio 2.8, p = 0.013) and LASct <14% (odds ratio 2.5, p = 0.045).Increased EAT thickness in subjects with obesity without known cardiac disease was independently associated with subclinical cardiac dysfunction. Our findings suggest that EAT might play a role in the early stages of cardiac dysfunction in obesity before this may progress to overt clinical disease.
Early left atrial venting versus conventional treatment for left ventricular decompression during venoarterial extracorporeal membrane oxygenation support: The <scp>EVOLVE‐ECMO</scp> randomized clinical trial
Authors: Hanbit Park, Jeong Hoon Yang, Jung‐Min Ahn, Do‐Yoon Kang, Pil Hyung Lee, Tae Oh Kim, Ki Hong Choi, Pil Je Kang, Sung‐Ho Jung, Sung‐Cheol Yun, Duk‐Woo Park, Seung‐Whan Lee, Seung‐Jung Park, Min‐Seok Kim
Journal: European Journal of Heart Failure (2023)
Gut microbiome diversity, variability, and latent community types compared with shifts in body weight during the freshman year of college in dormitory-housed adolescents
Authors: Alex E. Mohr, Mary M. Ahern, Dorothy D. Sears, Meg Bruening, Corrie M. Whisner
Journal: Gut Microbes (2023)

Significant human gut microbiome changes during adolescence suggest that microbial community evolution occurs throughout important developmental periods including the transition to college, a typical life phase of weight gain. In this observational longitudinal study of 139 college freshmen living in on-campus dormitories, we tracked changes in the gut microbiome via 16S amplicon sequencing and body weight across a single academic year. Participants were grouped by weight change categories of gain (WG), loss (WL), and maintenance (WM). Upon assessment of the community structure, unweighted and weighted UniFrac metrics revealed significant shifts with substantial variation explained by individual effects within weight change categories. Genera that positively contributed to these associations with weight change included Bacteroides, Blautia, and Bifidobacterium in WG participants and Prevotella and Faecalibacterium in WL and WM participants. Moreover, the Prevotella/Bacteroides ratio was significantly different by weight change category, with WL participants displaying an increased ratio. Importantly, these genera did not display co-dominance nor ease of transition between Prevotella- and Bacteroides-dominated states. We further assessed the overall taxonomic variation, noting the increased stability of the WL compared to the WG microbiome. Finally, we found 30 latent community structures within the microbiome with significant associations with waist circumference, sleep, and dietary factors, with alcohol consumption chief among them. Our findings highlight the high level of individual variation and the importance of initial gut microbiome community structure in college students during a period of major lifestyle changes. Further work is needed to confirm these findings and explore mechanistic relationships between gut microbes and weight change in free-living individuals.The freshman year of college is a transitional period that may provide insights into the relationship between the gut microbiome and body weight regulation due to the lifestyle changes that increase vulnerability to weight change. During this critical period many of the lifestyle factors that influence body weight formalize and have important bearing on health outcomes throughout an individual’s life. In this college-aged population, shifts in community structure and variability of gut microbes were different by weight change trajectory. Genera that underpinned these shifts such as Bacteroides, Blautia, Bifidobacterium, Prevotella, and Faecalibacterium displayed varying degrees of inter-individual variability and, in some instances, resistance to alternative states. Accounting for these considerations in the context of body weight control in adolescents may prove useful for improving target outcomes in an intervention setting.
Peripheral Airway Sarcoidosis: Seeing What Was Previously Invisible
Authors: Rocco Trisolini, Giuliana Pasciuto, Alessandra Cancellieri, Chiara Agrosì, Daniele Magnini, Luca Richeldi
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Peripheral Airway Sarcoidosis: Seeing What Was Previously Invisible." American Journal of Respiratory and Critical Care Medicine, 208(12), pp. 1328–1329
Prevalence of Cannabis Use Disorder and Reasons for Use Among Adults in a US State Where Recreational Cannabis Use Is Legal
Authors: Gwen T. Lapham, Theresa E. Matson, Jennifer F. Bobb, Casey Luce, Malia M. Oliver, Leah K. Hamilton, Katharine A. Bradley
Journal: JAMA Network Open (2023)

Medical and nonmedical cannabis use and cannabis use disorders (CUD) have increased with increasing cannabis legalization. However, the prevalence of CUD among primary care patients who use cannabis for medical or nonmedical reasons is unknown for patients in states with legal recreational use.To estimate the prevalence and severity of CUD among patients who report medical use only, nonmedical use only, and both reasons for cannabis use in a state with legal recreational use.This cross-sectional survey study took place at an integrated health system in Washington State. Among 108 950 adult patients who completed routine cannabis screening from March 2019 to September 2019, 5000 were selected for a confidential cannabis survey using stratified random sampling for frequency of past-year cannabis use and race and ethnicity. Among 1688 respondents, 1463 reporting past 30-day cannabis use were included in the study.Patient survey-reported reason for cannabis use in the past 30 days: medical use only, nonmedical use only, and both reasons.Patient responses to the Composite International Diagnostic Interview-Substance Abuse Module for CUD, corresponding to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition CUD severity (0-11 symptoms) were categorized as any CUD (≥2 symptoms) and moderate to severe CUD (≥4 symptoms). Adjusted analyses were weighted for survey stratification and nonresponse for primary care population estimates and compared prevalence of CUD across reasons for cannabis use.Of 1463 included primary care patients (weighted mean [SD] age, 47.4 [16.8] years; 748 [weighted proportion, 61.9%] female) who used cannabis, 42.4% (95% CI, 31.2%-54.3%) reported medical use only, 25.1% (95% CI, 17.8%-34.2%) nonmedical use only, and 32.5% (95% CI, 25.3%-40.8%) both reasons for use. The prevalence of CUD was 21.3% (95% CI, 15.4%-28.6%) and did not vary across groups. The prevalence of moderate to severe CUD was 6.5% (95% CI, 5.0%-8.6%) and differed across groups: 1.3% (95% CI, 0.0%-2.8%) for medical use, 7.2% (95% CI, 3.9%-10.4%) for nonmedical use, and 7.5% (95% CI, 5.7%-9.4%) for both reasons for use (P = .01).In this cross-sectional study of primary care patients in a state with legal recreational cannabis use, CUD was common among patients who used cannabis. Moderate to severe CUD was more prevalent among patients who reported any nonmedical use. These results underscore the importance of assessing patient cannabis use and CUD symptoms in medical settings.
Trends in Gestational Weight Gain in Louisiana, March 2019 to March 2022
Authors: Emily W. Harville, Chelsea L. Kracht, Nicole L. Cohen, Elizabeth F. Sutton, Maryam Kebbe, Leanne M. Redman
Journal: JAMA Network Open (2023)

Importance Average gestational weight gain (GWG) increased during the COVID-19 pandemic, but it is not known whether this trend has continued. Objective To examine patterns of GWG during the COVID-19 pandemic by delivery and conception timing through the second year of the pandemic. Design, Setting, and Participants This cohort study is a retrospective review of birth certificate and delivery records from 2019 to 2022. Electronic health records were from the largest delivery hospital in Louisiana. Participants included all individuals giving birth from March 2019 to March 2022. Data analysis was performed from October 2022 to July 2023. Exposure Delivery date (cross-sectionally) and conception before the pandemic (March 2019 to March 2020) and during the peak pandemic (March 2020 to March 2021) and late pandemic (March 2021 to March 2022). Main Outcomes and Measures The primary outcome was GWG (total GWG and adherence to the 2009 Institute of Medicine recommendations) analyzed using linear and log-linear regression with control for covariates. Results Among 23 012 total deliveries (8763 Black individuals [38.1%]; 11 774 White individuals [51.2%]; mean [SD] maternal age, 28.9 [5.6] years), 3182 individuals (42.0%) exceeded the recommended weight gain in the year proceeding the pandemic, 3400 (45.4%) exceeded recommendations during the peak pandemic, and 3273 (44.0%) exceeded recommendations in the late pandemic. Compared with those who delivered before the pandemic (reference), participants had higher total GWG if they delivered peak or late pandemic (adjusted β [SE], 0.38 [0.12] kg vs 0.19 [0.12] kg; P = .007). When cohorts were defined by conception date, participants who conceived before the pandemic but delivered after the pandemic started had higher GWG compared with those whose entire pregnancy occurred before the pandemic (adjusted β [SE], 0.51 [0.16] kg). GWG was lower in the pregnancies conceived after the pandemic started and the late pandemic (adjusted β [SE], 0.29 [0.12] kg vs 0.003 [0.14] kg; P = .003) but these participants began pregnancy at a slightly higher weight. Examining mean GWG month by month suggested a small decrease for March 2020, followed by increased mean GWG for the following year. Individuals with 2 pregnancies (1289 individuals) were less likely to gain weight above the recommended guidelines compared with their prepandemic pregnancy, but this association was attenuated after adjustment. Conclusions and Relevance In this cohort, individuals with critical time points of their pregnancy during the COVID-19 pandemic gained more weight compared with the previous year. The increased GWG leveled off as the pandemic progressed but individuals were slightly heavier beginning pregnancy.
A Phase II Trial of Rivoceranib, an Oral Vascular Endothelial Growth Factor Receptor 2 Inhibitor, for Recurrent or Metastatic Adenoid Cystic Carcinoma
Authors: Glenn J. Hanna, Myung-Ju Ahn, Jameel Muzaffar, Bhumsuk Keam, Daniel W. Bowles, Deborah J. Wong, Alan L. Ho, Sung-Bae Kim, Francis Worden, Tak Yun, Xianzhang Meng, Jan M. Van Tornout, Maureen G. Conlan, Hyunseok Kang
Journal: Clinical Cancer Research (2023)

Abstract Purpose: This open-label, single-arm, phase II study evaluated the vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitor (TKI) rivoceranib in patients with recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC). Patients and Methods: Eligible patients had confirmed disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) with ≥20% increase in radiologically or clinically measurable lesions or appearance of new lesions within the preceding 6 months. Patients received oral rivoceranib 700 mg once daily. Primary outcomes were objective response rate (ORR) by investigator review and by blinded independent review committee (BIRC). Results: Eighty patients were enrolled and 72 were efficacy evaluable. Seventy-four patients had distant metastases and 49 received prior systemic treatment (14 received VEGFR TKIs). Per investigator and BIRC, respectively, ORR was 15.3% [95% confidence interval (95% CI), 7.9–25.7] and 9.7% (95% CI, 4.0–19.0); median duration of response was 14.9 months (95% CI, 4.9–17.3) and 7.2 months (95% CI, 3.5–8.4); and median progression-free survival was 9.0 months (95% CI, 7.3–11.5) and 9.0 months (95% CI, 7.7–11.5). Grade ≥3 treatment-related adverse events occurred in 56 patients (70.0%); the most common were hypertension (34, 42.5%) and stomatitis (6, 7.5%). Four grade 5 events occurred with one attributed to rivoceranib (epistaxis). Sixty-eight patients (85.0%) had ≥1 dose modifications and 16 patients (20.0%) discontinued rivoceranib for toxicity. Conclusions: In patients with progressing R/M ACC, rivoceranib demonstrated antitumor activity and a manageable safety profile consistent with other VEGFR TKIs.
Rash and Poor Wound Healing After Mastectomy
Authors: Austinn C. Miller, Vladimir Ratushny, Armand B. Cognetta
Journal: JAMA (2023)

A patient who had recently undergone bilateral mastectomy had erythema, edema, pain, pruritus, serous fluid drainage at the incision sites, and an erythematous papulovesicular rash on the trunk and extremities. A skin swab bacterial culture result was negative, and the skin findings did not improve with antibiotics. What is the diagnosis and what would you do next?
The Unresolved Challenge of Triage
Authors: Barbara E. Bierer, Robert D. Truog
Journal: JAMA Network Open (2023)

Jackson S. Ennis, BA; Kirsten A. Riggan, MA, MS; Nicholas V. Nguyen, BA; Daniel B. Kramer, MD, MPH; Alexander K. Smith, MD, MS, MPH; Daniel P. Sulmasy, MD, PhD; Jon C. Tilburt, MD; Susan M. Wolf, JD; Erin S. DeMartino, MD